Porous material and methods related thereto

ABSTRACT

Disclosed herein is an aerogel made from a polyhydroxy benzene compound crosslinked with formaldehyde. The aerogel is dry and has a first volume and wherein the aerogel can be exposed to a liquid and be re-dried in a gas while retaining at least 70% of the first volume.

BACKGROUND

Historical routes to resorcinol-formaldehyde aerogels yield hydrogelswhich must be supercritically dried in order to retain their nano-porousproperties. Even after supercritical drying, exposure to liquids willcause catastrophic failure of the material. Several routes to air-driedaerogels have been published to yield material that can be processed anddried at atmospheric pressure, but have the same catastrophic failure asthe supercritically dried aerogel when exposed to liquids.

Phenol formaldehyde polymers have been studied for over 100 years. Acidcatalyzed polymers with excess phenol are called Novolacs and basecatalyzed polymers with excess formaldehyde are called Resoles.Resorcinol-formaldehyde aerogels were invented in the 1990s. The mostcommon catalyst is sodium carbonate (a base).

Paul Shu (U.S. Pat. No. 4,903,766 (1990)) uses aluminum acetate as acrosslinker for resorcinol and formaldehyde to form a gel that is usedto seal pores in oil wells. This application is an in-situ gel formationthat forms selectively in the porous structure around the oil well, butit does not forma n aerogel.

Accordingly, there is a need for aerogels that do not experiencecatastrophic failure when exposed to liquids. Disclosed herein are suchaerogels and methods related thereto.

BRIEF SUMMARY

Disclosed herein is an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume.

Also disclosed herein is a device comprising the aerogel disclosedherein.

Also disclosed herein is a method of making an aerogel comprising thesteps of: a) crosslinking a polyhydroxy benzene compound withformaldehyde in the presence of an aluminum catalyst, thereby forming agel having a first volume; and b) drying the gel in gas, thereby formingan aerogel having a second volume.

Also disclosed herein is a method of detecting a biological condition ina subject comprising the steps of: a) incubating a sample with anaerogel disclosed herein; and b) detecting the presence or absence of abiomarker for a biological condition in the sample using the signalingmoiety of the aerogel.

Also disclosed herein is a method comprising a) incubating a sampleobtained from a subject with an aerogel disclosed herein; and b)determining the presence or absence of a biomarker for a biologicalcondition in the sample using the signaling moiety of the aerogel,wherein the presence of the biomarker indicates the subject has abiological condition, wherein the absence of the biomarker indicates thesubject does not have a biological condition.

Additional advantages of the disclosed method and compositions will beset forth in part in the description which follows, and in part will beunderstood from the description, or may be learned by practice of thedisclosed method and compositions. The advantages of the disclosedmethod and compositions will be realized and attained by means of theelements and combinations particularly pointed out in the appendedclaims. It is to be understood that both the foregoing generaldescription and the following detailed description are exemplary andexplanatory only and are not restrictive of the invention as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate several embodiments of thedisclosed method and compositions and together with the description,serve to explain the principles of the disclosed method andcompositions.

FIG. 1 shows a schematic of a 3-electrode system.

FIGS. 2A, 2B, and 2C show cyclic voltammetry profiles for the threecarbon foams (C4502, C4501, and BQ001 respectively) that can be testedin aqueous electrolyte (0.5M H₂SO₄).

FIGS. 3A shows a Nyquist plot from Impedance spectroscopy, and FIG. 3Bshows Discharge profiles, Potential vs. Specific Capacity.

FIGS. 4A, 4B, 4C, and 4D show cyclic voltammetry profiles for the fourcarbon foams (C4502, C4501, BQ001, and BQ001 hydrophobic respectively)that can be tested in non-aqueous electrolyte (1M LiClO₄).

FIGS. 5A shows discharge profiles, Potential vs. Specific Capacity ofsamples C4501, BQ001, BQ001 hydrophobic and FIG. 5B shows dischargeprofiles of samples C4502.

FIGS. 6A and 6B show cyclic voltammetry profiles of carbon foam before(FIG. 6A) and after (FIG. 6B) polymer deposition for 2.68 C at 14 mA andFIG. 6C shows a Nyquist plot of real and imaginary impedance comparingbefore and after deposition.

FIGS. 7A and 7B show cyclic voltammetry profiles of carbon foam before(FIG. 7A) and after (FIG. 7B) polymer deposition for 13.4 C at 14 mA(reducing current up to 6 mA) and FIG. 7C shows a Nyquist plot of realand imaginary impedance comparing before and after deposition.

FIGS. 8A and 8B show a carbon foam characterized with Cyclic Voltammetryin 0.5M H2SO4 aqueous solution, and FIG. 8C shows discharge profiles ofthe carbon foam-sample mass 2.79 mg.

FIGS. 9A and 9B show a carbon foam characterized with Cyclic Voltammetryin 1M LiClO₄ in Propylene Carbonate, and FIG. 9C shows dischargeprofiles of the carbon foam-sample mass 1.82 mg.

FIGS. 10A and 10B show a carbon foam characterized with CyclicVoltammetry in 6M KOH aqueous solution—total mass 1.00 mg.

FIGS. 11A, 11B, 11C, and 11D show a carbon Foam+PPy: Cyclic Voltammetrypolymerization of pyrrole on carbon foam. Plain carbon foam mass: 5.13mg(FIG. 11A and 11B) after polymerization of polypyrrole on its surface8.94mg (FIG. 11C and 11D), 11A and 11B are before polymerization; 11Cand 11D are after polymerization.

FIGS. 12A, 12B, and 12C show three standard representations of lateralflow immunoassays. The most common lateral flow devices can be read byeye (FIG. 12B), while commercial readers have recently appeared toimpart quantitation (FIG. 12C). Their sensitivities are typically notsignificantly superior to those read by eye, though they do provide somemeasure of quantitation, if the assay is designed to function as such.

FIGS. 13A and 13B show a representation of lateral flow eye-readability.FIG. 13A shows the assay as limited by background from a whitenitrocellulose membrane in a traditional AuNP lateral flow assay. InFIG. 13B, the dotted line represents the interference of backgroundscattering, severely limiting the sensitivity of the assay.

FIG. 14 is a SEM micrograph of one formulation of RF aerogel aftercarbonization, as produced by SRI. The pore size and optical density ofthe material can be adjusted over a wide range with simple processingtechniques.

FIG. 15 shows miRNA detection by FRET on an aerogel substrate.

FIGS. 16A and 16B show a proposed Click chemistry of labeling aerogelfor FRET use.

FIG. 17 is a diagram of initial optical evaluation setup in phase I.Collimation can be adjusted evaluate efficacy of filters at varyingnumerical apertures, as a compact system will trade collimation forcomplexity.

DETAILED DESCRIPTION

The disclosed method and compositions may be understood more readily byreference to the following detailed description of particularembodiments and the Example included therein and to the Figures andtheir previous and following description

It is to be understood that the disclosed method and compositions arenot limited to specific synthetic methods, specific analyticaltechniques, or to particular reagents unless otherwise specified, and,as such, may vary. It is also to be understood that the terminology usedherein is for the purpose of describing particular embodiments only andis not intended to be limiting.

Materials

Disclosed are materials, compositions, and components that can be usedfor, can be used in conjunction with, can be used in preparation for, orare products of the disclosed method and compositions. These and othermaterials are disclosed herein, and it is understood that whencombinations, subsets, interactions, groups, etc. of these materials aredisclosed that while specific reference of each various individual andcollective combinations and permutation of these compounds may not beexplicitly disclosed, each is specifically contemplated and describedherein. For example, if an aerogel is disclosed and discussed and anumber of modifications that can be made to a number of materialsincluding the aerogel, then each and every combination and permutationof the aerogel and the modifications that are possible are specificallycontemplated unless specifically indicated to the contrary. Thus, if aclass of molecules A, B, and C are disclosed as well as a class ofmolecules D, E, and F and an example of a combination molecule, A-D isdisclosed, then even if each is not individually recited, each isindividually and collectively contemplated. Thus, is this example, eachof the combinations A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F arespecifically contemplated and should be considered disclosed fromdisclosure of A, B, and C; D, E, and F; and the example combination A-D.Likewise, any subset or combination of these is also specificallycontemplated and disclosed. Thus, for example, the sub-group of A-E,B-F, and C-E are specifically contemplated and should be considereddisclosed from disclosure of A, B, and C; D, E, and F; and the examplecombination A-D. This concept applies to all aspects of this applicationincluding, but not limited to, steps in methods of making and using thedisclosed compositions. Thus, if there are a variety of additional stepsthat can be performed it is understood that each of these additionalsteps can be performed with any specific embodiment or combination ofembodiments of the disclosed methods, and that each such combination isspecifically contemplated and should be considered disclosed.

A. Definitions

As used herein, the term “subject” or “patient” refers to any organismto which a composition of this invention may be administered, e.g., forexperimental, diagnostic, and/or therapeutic purposes. Typical subjectsinclude animals (e.g., mammals such as non-human primates, and humans;avians; domestic household or farm animals such as cats, dogs, sheep,goats, cattle, horses and pigs; laboratory animals such as mice, ratsand guinea pigs; rabbits; fish; reptiles; zoo and wild animals) and/orplants. Typically, “subjects” are animals, including mammals such ashumans and primates; and the like.

The term “biomarker” refers to a measurable substance in a sample,wherein the presence of the substance is indicative of a disease,infection, or environmental exposure. In some instances, a biomarker canbe indicative of how a subject will respond to a particular treatment

The term “sample” refers to any biological substance. In some instances,the sample can be a human sample. For example, human samples can be butare not limited to, urine, blood, plasma, saliva, sweat, feces, mucus,semen, vaginal fluids, ocular fluids, cells, cell lysates, proteins,DNA, RNA, metabolites, or tissue. In some instances, the biologicalsample can be an environmental sample. For example, environmentalsamples can be but are not limited, soil, water, particulates in theair, and food.

The term “hydrophobic” refers to a material, such as an aerogel, thatdoes not absorb water.

The term “hydrophilic” refers to a material, such as an aerogel, thatwicks water into the material, such as an aerogel.

B. Aerogels

Disclosed herein is an air-dried aerogel, such as a resorcinolformaldehyde low density aerogel. The aerogel can have a broad range ofpore sizes, such as, for example, from a few nanometers to severalmicrons. The surface characteristics of the aerogel can be modified tomake the material highly hydrophilic or hydrophobic. In one aspect, theaerogel can be modified in dried form. In one aspect, the aerogel can belyophilic. The aerogel disclosed herein can be wet and re-dried whileretaining its structure, volume, and integrity. The disclosed aerogelcan be used in several devices, including a medical device, athermoelectric device, an acoustic device, a thermal protection device,in aerospace structures, a water purification device, a chemicalseparation device, an electrical device, or other specializedapplications.

The disclosed aerogels can be made in and can have the same densityrange as prior resorcinol-formaldehyde aerogels (˜100 mg/cc) and can becarbonized in a similar fashion to conventional aerogels. Conventionalaerogels requires washing with an organic solvent and supercriticaldrying. However, researchers have attempted to develop air-dryingroutes, however organic washing to prevent densification prior to dryingis still commonly required in these processes. Contrary to conventionalaerogels, the disclosed aerogels can be made a gas-dried solid with verylittle shrinkage (i.e. reduction of volume) directly with no washingstep. As such, the disclosed aerogel can be wet multiple times it's masswith water or oil without changing shape or losing integrity.

With a polar liquid, such as water, several wetting and drying cyclescan be performed on the same specimen. The conventional supercritically-dried aerogels will wet with water, but they fall apart upondrying after wetting. The disclosed aerogel's unique wetting ability canallow it to be modified after drying for use in many applications thatwould cause state of the art aerogels to fail—for example, be coated forthermal protection systems, modified for carbon capture systems,modified for specific water remediation systems, coated forincorporation into thermo-electric generators, or utilized in cellscaffolding systems.

Accordingly, disclosed herein is an aerogel comprising a polyhydroxybenzene compound crosslinked with formaldehyde, wherein the aerogel isdry and has a first volume, wherein the aerogel can be exposed to aliquid and be re-dried in a gas while retaining at least 70% of thefirst volume.

In one aspect, the polyhydroxy benzene compound is a dihydroxy benzenecompound. In another aspect, the dihydroxy benzene compound is selectedfrom the group consisting of resorcinol and catechol or a combinationthereof. For example, the dihydroxy benzene compound can be resorcinol.In another example, the dihydroxy benzene compound can be catechol.

In one aspect, the molar ratio of the polyhydroxy benzene compound toformaldehyde in the aerogel is from about 1:1 to about 1:4. For example,the molar ratio of the polyhydroxy benzene compound to formaldehyde inthe aerogel is from about 1:1 to about 1:3. In another example, themolar ratio of the polyhydroxy benzene compound to formaldehyde in theaerogel is from about 1:1.5 to about 1:2.5. In yet another example, themolar ratio of the polyhydroxy benzene compound to formaldehyde in theaerogel is about 1:2.

In one aspect, the molar ratio of the resorcinol to formaldehyde in theaerogel is from about 1:1 to about 1:4. For example, the molar ratio ofthe resorcinol to formaldehyde in the aerogel is from about 1:1 to about1:3. In another example, the molar ratio of the resorcinol toformaldehyde in the aerogel is from about 1:1.5 to about 1:2.5. In yetanother example, the molar ratio of the resorcinol to formaldehyde inthe aerogel is about 1:2.

The aerogel disclosed herein does not suffer the catastrophic failurewhen exposed to a liquid and re-dried in a gas, such as air or inertgas, like conventional aerogels. Accordingly, the aerogel can be wet andre-dried in a gas, such as air or inert gas, at least 1, 2, 3, 5, 10,20, 30, 50, 75, or 100 times while retaining its volume. For example,the aerogel can be wet and re-dried in a gas, such as air or inert gas,from 1 to 100 while retaining its volume. In one aspect, the aerogel hasbeen wet and re-dried in a gas, such as air or inert gas, at least 1, 2,3, 5, 10, 20, 30, 50, 75, or 100 times while retaining its volume. Forexample, in some aspects, the aerogel has been wet and re-dried in agas, such as air or inert gas, from 1 to 100 while retaining its volume.In one aspect, the aerogel can be wet with a polar liquid and bere-dried. Examples of suitable polar liquids include, but are notlimited to, water, alcohols, such as methanol, ethanol, propanol, aceticacid, ammonia, acetonitrile, dimethyl sulfoxide, or N,N-diformamide. Thepolar liquid, in one aspect, can be water. In another aspect, theaerogel can be wet with a non-polar liquid and be re-dried. Examples ofsuitable non-polar liquids include, but are not limited to, oils,pentane, hexane, cyclohexane, benzene, toluene, chloroform, diethylether. The non-polar liquid, in one aspect, can be an oil.

In one aspect, the aerogel can be exposed to a liquid and be re-dried ina gas while retaining at least 75% of the first volume. In anotheraspect, the aerogel can be exposed to a liquid and be re-dried in a gaswhile retaining at least 80% of the first volume. In yet another aspect,the aerogel can be exposed to a liquid and be re-dried in a gas whileretaining at least 85% of the first volume. In yet another aspect, theaerogel can be exposed to a liquid and be re-dried in a gas whileretaining at least 90% of the first volume. In yet another aspect, theaerogel can be exposed to a liquid and be re-dried in a gas whileretaining at least 95% of the first volume. In yet another aspect, theaerogel can be exposed to a liquid and be re-dried in a gas whileretaining at least 97% of the first volume. In yet another aspect, theaerogel can be exposed to a liquid and be re-dried in a gas whileretaining at least 98% of the first volume. In yet another aspect, theaerogel can be exposed to a liquid and be re-dried in a gas whileretaining at least 99% of the first volume. In yet another aspect, theaerogel can be exposed to a liquid and be re-dried in a gas whileretaining at least 99.9% of the first volume.

In one aspect, the aerogel is a functionalized aerogel. A functionalizedaerogel is an aerogel that has been chemically modified from itsoriginal form. For example, the hydroxyl groups (—OH) on the aerogel canbe used to bond a chemical linker to the aerogel to produce afunctionalized aerogel. For example, an acyl halide moiety on a chemicallinker can be reacted with a hydroxyl group on the aerogel to form anester bond to bond the chemical linker to the aerogel.

In one aspect, the chemical linker modifies the surface properties ofthe hydrogel. For example, a hydrophilic aerogel can be modified tobecome hydrophobic by using an alkane type chemical linker. In anotheraspect, the chemical linker comprises a reactive moiety. The reactivemoiety can be used to bond other molecules to the linker and in turn tothe aerogel. For example, the chemical linker can comprise an amine, anamide, a silane, an azide, an alkane, an alkene, an alkyne, or a thiol.The amine, amide, silane, azide, alkane, alkene, alkyne, or thiol can beused to attach bond other molecules to the linker and in turn to theaerogel. For example, the linker can be an amine, which can be used forcarbon capture applications. In another example, the linker can be asilane, which can be used for hydrophobic application. Silanes can alsobe used to convert the aerogel to a ceramic material. In yet anotherexample, the chemical linker can be an alkyne, which can be used in lifescience applications. In one aspect, the chemical linker is or is bondedto a polymer. In one aspect, the linker comprises an azide that can beused to bond a signaling moiety. Thus, in one aspect, the functionalizedaerogel comprises the aerogel, a chemical linker, and a signalingmoiety, wherein the chemical linker is bound to both the signalingmoiety and the aerogel.

As such, the aerogels can be modified for a particular purpose. Forexample, the aerogel can be modified with a chemical linker comprising athiol moiety if gold is to be attached to the aerogel. In anotherexample, the aerogel can be modified with an alkyl group if ahydrophobic aerogel is desired. In other application, it may be desiredto not modify the aerogel to retain the hydrophobicity and absorptivecapabilities of the aerogel, for example, in a medical device to absorbbodily fluids, such as blood, from a wound.

In one aspect, the signaling moiety comprises a detection portion and atarget binding portion. In one aspect, a detection portion allows forthe aerogel or a portion of the aerogel to be detected. In one aspect,the signaling moiety, in particular the detection portion, can comprisea fluorescent moieties, colloidal gold, enzymes, dyes, radioisotopes, orchemiluminescent markers For example, the detection portion can comprisefluorescence resonance energy transfer (FRET). In one aspect, a targetbinding portion allows for binding of the signaling moiety to a target,or a specific molecule, in a sample. In one aspect, a target bindingportion comprises a RNA molecule, a DNA molecule, an antibody orfragment thereof, or known receptors to biomarkers.

In one aspect, the aerogel is carbonized. The aerogel can be carbonizedby conventional methods at elevated temperatures. A carbonized aerogelis suitable for use in electrical devices, for example capacitancedevices, and thermal devices. The carbonized aerogel can also besuitable for water treatment applications due to the large surface areafor microorganism adsorption or preferential absorption devices. Thecarbonization of aerogels is described by Tamon et al. Carbon, Vol. 36,No. 9, pp 1257-1262 (1998), which is incorporated herein by reference,particularly for its disclosure of carbonization of aerogels.

In one aspect, the aerogel is capable of absorbing up to ten times itsmass of a polar liquid or a non-polar liquid. For example, the aerogelis capable of absorbing from six times to ten times its mass of a polarliquid or a non-polar liquid. In another example, the aerogel is capableof absorbing from seven times to ten times its mass of a polar liquid ora non-polar liquid. In another example, the aerogel is capable ofabsorbing from eight times to ten times its mass of a polar liquid or anon-polar liquid. In yet another example, the aerogel is capable ofabsorbing from nine times to ten times its mass of a polar liquid or anon-polar liquid. In yet another example, the aerogel is capable ofabsorbing ten times its mass of a polar liquid or a non-polar liquid.Examples of suitable polar liquids include, but are not limited to,water, alcohols, such as methanol, ethanol, propanol, acetic acid,ammonia, acetonitrile, dimethyl sulfoxide, or N, N-diformamide. Thepolar liquid, in one aspect, can be water. In another aspect, theaerogel can be wet with a non-polar liquid and be re-dried. Examples ofsuitable non-polar liquids include, but are not limited to, oils,pentane, hexane, cyclohexane, benzene, toluene, chloroform, diethylether. The non-polar liquid, in one aspect, can be an oil.

C. Method of Making Aerogels

Also disclosed herein are methods of making the disclosed aerogels. Alsodisclosed herein are aerogels made by the method disclosed herein.

The aerogels disclosed herein can be made by crosslinking polyhydroxybenzene compound with formaldehyde in the presence of an aluminumcatalyst. The crosslinking can take place in a degassed and deionizedwater solution. The aerogel is then dried in gas, such as for example,air or inert gas. The use of an aluminum catalyst produces the aerogelsdisclosed herein with the desired properties not achieved inconventional aerogels made by conventional methods.

Accordingly, disclosed herein is a method of making an aerogelcomprising the steps of: a) crosslinking a polyhydroxy benzene compoundwith formaldehyde in the presence of an aluminum catalyst, therebyforming a gel having a first volume; and b) drying the gel in gas,thereby forming an aerogel having a second volume.

In one aspect, the step of crosslinking a polyhydroxy benzene compoundwith formaldehyde in the presence of an aluminum catalyst, therebyforming a gel having a first volume can be performed in a watersolution. The water solution can be a degassed and deionized watersolution.

In one aspect, the method further comprises further comprises the stepof modifying the aerogel with a chemical linker disclosed herein.

Also disclosed herein is a method comprising the steps of: a) providingan aerogel produced by a method disclosed herein; and b) modifying theaerogel with a chemical linker disclosed herein.

The modifying step of the aerogel can be performed when the aerogel isin a solid dry form. In one aspect, an acyl halide group on the chemicallinker is reacted with an hydroxyl group on the aerogel to bind thechemical linker to the aerogel via an ester group.

In one aspect, the gas is air. In another aspect, the gas is an inertgas. Suitable inert gases include, but are not limited to, nitrogen andargon.

In one aspect, the step of drying the gel in gas comprises exposing thegel to air having a temperature from about 70° C. to about 120° C. Inanother aspect, the step of drying the gel in gas comprises exposing thegel to gas having a temperature from about 70° C. to about 100° C. Inyet another aspect, the step of drying the gel in gas comprises exposingthe gel to gas having a temperature from about 80° C. to about 90° C.

In one aspect, the drying step is performed for at least 6 hours, 12hours, 1 day, 3 days, 5 days, 7 days, 10 days, or 20 days. For example,the drying step can be performed from 6 hours to 20 days, for example,from 1 day to 10 days.

Thus, for example, the step of drying the gel in gas comprises exposingthe gel to air having a temperature from about 70° C. to about 120° C.from 6 hours to 10 days.

In one aspect, the polyhydroxy benzene compound is a dihydroxy benzenecompound. In another aspect, the dihydroxy benzene compound is selectedfrom the group consisting of resorcinol and catechol or a combinationthereof. For example, the dihydroxy benzene compound can be resorcinol.In another example, the dihydroxy benzene compound can be catechol.

In one aspect, the second volume is at least 70% of the first volume. Inanother aspect, the second volume is at least 80% of the first volume.In yet another aspect, the second volume is at least 85% of the firstvolume. In yet another aspect, the second volume is at least 90% of thefirst volume. In yet another aspect, the second volume is at least 95%of the first volume. In yet another aspect, the second volume is atleast 97% of the first volume. In yet another aspect, the second volumeis at least 98% of the first volume. In yet another aspect, the secondvolume is at least 99% of the first volume. In yet another aspect, thesecond volume is at least 99.9% of the first volume.

The aluminum catalyst can be in the form of an aluminum salt or aluminumproduced from an aluminum electrode. Accordingly, in one aspect, thealuminum catalyst comprises an aluminum salt catalyst. Suitable aluminumsalts include, but are not limited to aluminum acetate, aluminumcitrate, aluminum chloride, or aluminum oxide or a combination thereof.For example, the aluminum salt can comprise aluminum acetate.

In one aspect, aluminum catalyst can be mixed with a sodium catalyst,such as a sodium salt. Suitable sodium catalysts, such as sodium salts,that can be mixed with the aluminum catalyst include, but are notlimited to sodium acetate, sodium hydroxide, sodium tetraborate, andsodium lingosulfonate.

In another aspect, the aluminum catalyst is aluminum produced from analuminum electrode at a voltage. In one aspect, the aluminum catalyst isaluminum produced from an aluminum electrode at a voltage from 20V to100V. For example, the aluminum catalyst can aluminum produced from analuminum electrode at a voltage from 20V to 80V. In another example, thealuminum catalyst can aluminum produced from an aluminum electrode at avoltage from 20V to 60V.

The crosslinking of the polyhydroxy benzene compound with formaldehydecan take place in a solvent. The solvent can have a pH that is neutralor acidic. In one aspect, the crosslinking of the polyhydroxy benzenecompound with formaldehyde can take place in a solvent having a pH ofabout 3 to about 7. In another aspect, the crosslinking of thepolyhydroxy benzene compound with formaldehyde can take place in asolvent having a pH of about 4 to about 6. In yet another aspect, thesolvent can have a pH that is basic. In yet another aspect, thecrosslinking of the polyhydroxy benzene compound with formaldehyde cantake place in a solvent having a pH of about 7 to about 12.

The solvent of the crosslinking can be a polar solvent. In one aspect,the solvent of the crosslinking comprises water.

The polyhydroxy benzene compound and formaldehyde can be mixed atvarious ratios. In one aspect, the molar ratio of the polyhydroxybenzene compound to formaldehyde in the crosslinking step is from about1:1 to about 1:4. In another aspect, the molar ratio of the polyhydroxybenzene compound to formaldehyde in the crosslinking step is from about1:1 to about 1:3. In yet another aspect, the molar ratio of thepolyhydroxy benzene compound to formaldehyde in the crosslinking step isfrom about 1:1.5 to about 1:2.5.

D. Methods of Detecting a Biological Condition

Disclosed are methods of detecting a biological condition in a subjectusing any of the disclosed aerogels. A biological condition, asdescribed herein, refers to any condition that has a circulating ordetectable biomarker. In some instances, a biological condition can be adisease, a disorder, an infection, or an environmental exposure.Biological conditions can be brought about by environmental factors,genetic factors, or a combination thereof. Examples of environmentalfactors can be, but are not limited to, air and water pollutants, metaltoxicity, radiation, stress, temperature, or infectious agents. In someinstances, a biological condition can be, but is not limited to,radiation sickness, heavy metal poisoning, cancer, autoimmune disorders,embryological or developmental disorders, parasitic infection, viralinfection, or bacterial infection. Circulating or detectable biomarkerscan be, but are not limited to, nucleic acids, proteins, metals,metabolites, or a combination thereof. For example, if the biologicalcondition is radiation exposure, biomarkers can be, but are not limitedto, amylase, diamine oxidase, Flt3L, citrulline, gamma-H2AX, p53, TRAILreceptor 2, FHL2, cyclin G, cyclin protein gene, or a combinationthereof. If the biological condition is a viral infection, biomarkerscan be, but are not limited to, myxovirus resistance A (MxA), C-reactiveprotein (CRP), cytokines, chemokines, specific miRNAs or a combinationthereof

Disclosed are methods comprising incubating a sample obtained from asubject with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, wherein the signaling moiety comprisesa detection portion and a target binding portion, and determining thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel, wherein the presenceof the biomarker indicates the subject has a biological condition,wherein the absence of the biomarker indicates the subject does not havea biological condition.

Disclosed are methods comprising incubating a sample obtained from asubject with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, wherein the signaling moiety comprisesa detection portion and a target binding portion, and determining thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel, wherein the presenceof the biomarker indicates the subject has a biological condition,wherein the absence of the biomarker indicates the subject does not havea biological condition, wherein the signaling moiety provides a positivesignal in the presence of the biomarker. In some instances, the positivesignal can be a fluorescent signal. In some instance, a positive signalis determined by running a control wherein there is no sample added andtherefore there is no biomarker present to bind to the target bindingportion. If the sample provides a signal that is higher than or morethan that seen in the control then there is a positive signal and therewas biomarker present in the sample.

Disclosed are methods comprising incubating a sample obtained from asubject with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, wherein the signaling moiety comprisesa detection portion and a target binding portion, and determining thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel, wherein the presenceof the biomarker indicates the subject has a biological condition,wherein the absence of the biomarker indicates the subject does not havea biological condition, wherein the biomarker is a nucleic acid, proteinor metal. In some instances, a nucleic acid can be miRNA. In someinstances, a nucleic acid can be DNA.

Disclosed are methods comprising incubating a sample obtained from asubject with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, wherein the signaling moiety comprisesa detection portion and a target binding portion, and determining thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel, wherein the presenceof the biomarker indicates the subject has a biological condition,wherein the absence of the biomarker indicates the subject does not havea biological condition, wherein the target binding portion binds to thebiomarker. A target binding portion can be anything that binds to abiomarker. For example, a target binding portion can be, but is notlimited to, a nucleic acid, protein, or metal chelators (e.g. EDTA). Insome instances, a target binding portion comprises a RNA molecule, a DNAmolecule, an antibody or fragment thereof, anti-microbial peptides suchas cathelicidins, charged metals such as nickel (binds to Histadineresidues on proteins) or iron (binds to proteins with heme-components)or known receptors to biomarkers.

Disclosed are methods comprising incubating a sample obtained from asubject with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, wherein the signaling moiety comprisesa detection portion and a target binding portion, and determining thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel, wherein the presenceof the biomarker indicates the subject has a biological condition,wherein the absence of the biomarker indicates the subject does not havea biological condition, wherein the biological condition is aninfectious disease, autoimmune disease, radiation exposure, or a geneticdisorder.

Disclosed are methods comprising incubating a sample obtained from asubject with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, wherein the signaling moiety comprisesa detection portion and a target binding portion, and determining thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel, wherein the presenceof the biomarker indicates the subject has a biological condition,wherein the absence of the biomarker indicates the subject does not havea biological condition, wherein the sample is blood.

E. Method of Detecting a Biomarker

Disclosed are methods of detecting a biomarker for a biologicalcondition in the sample using the aerogels disclosed above.

Disclosed are methods of detecting comprising the steps of incubating asample with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, wherein the signaling moiety comprisesa detection portion and a target binding portion, and detecting thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel,. The signaling moietyis a moiety that can be detected directly or indirectly. For example, asignaling moiety, specifically the detection portion, can be, but is notlimited to, colorimetric indicators, fluorescent moieties, colloidalgold, enzymes, dyes, detection by refractive index, radioisotopes, orchemiluminescent markers. In some instances, direct detection of asignaling moiety can occur when the binding of the biomarker to thetarget binding portion triggers a reaction that causes the detectionportion to be detected. For example, binding of the biomarker to thetarget binding portion can change the conformation of the detectionportion which allows for the detection portion to emit a signal and bedetected. In some instances, indirect detection of a signaling moietyoccurs when the detection portion requires something other than simplythe binding of the biomarker to the target binding portion in order forthe detection portion to be detected. For example, binding of thebiomarker to the target binding portion can result in a conformationalchange of the detection portion which can then be bound by a labeledantibody that binds only to the new conformational shape wherein thelabeled antibody bound to the detection portion can be detected.

Disclosed are methods of detecting comprising the steps of incubating asample with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, and detecting the presence or absenceof a biomarker for a biological condition in the sample using thesignaling moiety of the aerogel, wherein detecting the presence of thebiomarker comprises a positive signal provided from the signaling moietyof the aerogel. In some instance, a positive signal is determined byrunning a control wherein there is no sample added and therefore thereis no biomarker present to bind to the target binding portion. If thesample provides a signal that is higher than or more than that seen inthe control then there is a positive signal and there was biomarkerpresent in the sample.

Disclosed are methods of detecting comprising the steps of incubating asample with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, and detecting the presence or absenceof a biomarker for a biological condition in the sample using thesignaling moiety of the aerogel, wherein detecting the absence of thebiomarker comprises a negative signal or lack of signal provided fromthe signaling moiety of the aerogel. In some instance, a negative signalor lack of signal is determined by running a control wherein there is nosample added and therefore there is no biomarker present to bind to thetarget binding portion. The control would result in a negative signal orlack of signal. Thus, if the sample is the same as the control, thenthere was no biomarker present in the sample.

Disclosed are methods of detecting comprising the steps of incubating asample with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, and detecting the presence or absenceof a biomarker for a biological condition in the sample using thesignaling moiety of the aerogel, wherein the sample is blood.

Disclosed are methods of detecting comprising the steps of incubating asample with an aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume,wherein the aerogel is a functionalized aerogel, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel, and detecting the presence or absenceof a biomarker for a biological condition in the sample using thesignaling moiety of the aerogel, wherein the biomarker is a nucleicacid, protein or metal. In some instances, a nucleic acid can be miRNA.In some instances, a nucleic acid can be DNA.

F. Uses

Also disclosed herein are methods of using the aerogel disclosed herein.In one aspect, the aerogel can be a hydrophilic aerogel. The hydrophilicaerogel can be applied to a wound of a subject, wherein the hydrophilicaerogel absorbs bodily fluids, such as blood and/or pus, from the wound.

In another aspect, the aerogel can be carbonized and can be applied inan electrical device that performs as a capacitor.

In another aspect, the aerogel can be modified for applications inthermal or acoustic applications, such as, for example, insulation fromheat or noise.

In yet another aspect, the aerogel can be carbonized and placed in awater treatment system. Microorganism can adsorb to the carbonizedaerogel, which has a high surface area, and promote water treatment.Organic material in the water can also be adsorbed onto the carbonizedaerogel.

In another aspect, the aerogel, due to its 3D nature, can be used torecreate a 3D environment to study cellular physiology in mixed cellcultures. This system can be used for basic research, manufacturing,processing or implantation as individual cells, tissues, or wholeorgans. Cells can be seeded and cultured on the aerogel.

In another aspect, the aerogel can act as a probe to trap to abiomarker. In some instances, it can act as a filter. In some instances,extraneous and non-target biologicals can be retained or filteredthrough the aerogel based on size and adhesive properties. Because ofthe signaling moiety (e.g. fluorescent design) of the aerogel, onlybiological/chemical material (i.e. biomarker of interest) can bind tothe probe and can be detected by light excitation.

G. Devices

Also disclosed herein are devices comprising the aerogel disclosedherein. In one aspect, the device comprises a hydrophilic aerogeldisclosed herein. In another aspect, the device comprises a hydrophobicaerogel disclosed herein. In yet another aspect, the device comprises acarbonized aerogel disclosed herein. In yet another aspect, the devicecomprises a functionalized aerogel disclosed herein.

In one aspect, the device is a medical device. The medical device can beused to absorb absorbs bodily fluids, such as blood and/or pus, from thewound. Thus, for example, the device can be a wound dressing. Theaerogel, in these aspects, can be a hydrophilic aerogel.

In one aspect, the device can be a three dimensional porous structure towhich cells are seeded and cultured to facilitate a three dimensionalstructure while allowing for media stay in contact with, and preventgeneral necrosis of, the cultured cells. This device could be coatedwith signaling molecules using linking chemistry.

In one aspect, the device can be a water purification device. In oneexample, the water purification device can be a water treatment plant.In another example, water purification device can comprise a container,such as, for example a bottle. The water purification device can, inthese aspects, can be configured to filter or contact water prior to useby a consumer. The aerogel, in these aspects, can be a carbonizedaerogel. Thus, in one aspect, the device is a membrane distillationdevice.

In one aspect, the device can be a chemical separation device. Thedevice and aerogel can be configured to allow for selective adsorptionor absorption of chemicals into the aerogel. The chemical can also, insome aspects, bind to the aerogel. The adsorption and or absorption ofselected chemicals allows for chemical of these chemical from a mixtureof chemicals.

In one aspect, the device can be an electrical device. The aerogel, inthese aspects, can be a carbonized aerogel. The electrical device can bea capacitor. The electrical device can also be a thermo-electricaldevice.

In one aspect, the device is a device for insulation, such as thermal oracoustic insulation device. The aerogel can be one or more layers in amulti-layer insulation device.

In one aspect, the device is configured to be used to capture carbon.

Aspects

In view of the disclosure herein below are described certain moreparticularly described aspects of the inventions. These particularlyrecited aspects should not however be interpreted to have any limitingeffect on any different claims containing different or more generalteachings described herein, or that the “particular” aspects are somehowlimited in some way other than the inherent meanings of the language andformulas literally used therein.

Aspect 1: An aerogel comprising a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein the aerogel is dry and has afirst volume, wherein the aerogel can be exposed to a liquid and bere-dried in a gas while retaining at least 70% of the first volume.

Aspect 2: The aerogel of aspect 1, wherein the aerogel is hydrophilic.

Aspect 3: The aerogel of aspect 1, wherein the aerogel is hydrophobic.

Aspect 4: The aerogel of any one of aspects 1-3, wherein the aerogel isa functionalized aerogel.

Aspect 5: The aerogel of aspect 4, wherein the functionalized aerogelcomprises the aerogel and a chemical linker.

Aspect 6: The aerogel of aspect 5, wherein the chemical linker comprisesan ester or ether bond.

Aspect 7: The aerogel of aspects 5 or 6, wherein the chemical linkercomprises a reactive moiety.

Aspect 8: The aerogel of any one of aspects 4-7, wherein the chemicallinker comprises an amine, an amide, a silane, an azide, an alkane, analkene, an alkyne, or a thiol.

Aspect 9: The aerogel of any one of aspects 4-8, wherein thefunctionalized aerogel comprises the aerogel, a chemical linker, and asignaling moiety, wherein the chemical linker is bound to both thesignaling moiety and the aerogel.

Aspect 10: The aerogel of aspect 9, wherein the signaling moietycomprises a detection portion and a target binding portion.

Aspect 11: The aerogel of aspect 10, wherein the detection portioncomprises fluorescence resonance energy transfer (FRET).

Aspect 12: The aerogel of any one of aspects 1-11, wherein thepolyhydroxy benzene compound is a dihydroxy benzene compound.

Aspect 13: The aerogel of aspect 12, wherein the dihydroxy benzenecompound is selected from the group consisting of resorcinol andcatechol or a combination thereof

Aspect 14: The aerogel of aspects 12, wherein the dihydroxy benzenecompound is resorcinol.

Aspect 15: The aerogel of any one of aspects 1-14, wherein the molarratio of the polyhydroxy benzene compound to formaldehyde in the aerogelis from about 1:1 to about 1:4.

Aspect 16: The aerogel of any one of aspects 1-15, wherein the aerogelhas been exposed to a liquid and been re-dried in air.

Aspect 17: The aerogel of aspect 16, wherein the liquid is a non-polarliquid.

Aspect 18: The aerogel of aspect 16, wherein the liquid is a polarliquid.

Aspect 19: The aerogel of any one of aspects 1-18, wherein the aerogelcan be exposed to a liquid and be re-dried in air while retaining atleast 90% of the first volume.

Aspect 20: A method of making an aerogel comprising the steps of: a)crosslinking a polyhydroxy benzene compound with formaldehyde in thepresence of an aluminum catalyst, thereby forming a gel having a firstvolume; and b) drying the gel in gas, thereby forming an aerogel havinga second volume.

Aspect 21: The method of aspect 20, wherein the polyhydroxy benzenecompound is a dihydroxy benzene compound.

Aspect 22: The method of aspect 21, wherein the dihydroxy benzenecompound is selected from the group consisting of resorcinol andcatechol or a combination thereof

Aspect 23: The method of aspect 21, wherein the dihydroxy benzenecompound is resorcinol.

Aspect 24: The method of any one of aspects 20-23, wherein the aluminumcatalyst is an aluminum salt catalyst.

Aspect 25: The method of aspect 24, wherein the aluminum salt catalystcomprises aluminum acetate, aluminum citrate, aluminum chloride, oraluminum oxide or a combination thereof

Aspect 26: The method of aspects 24, wherein the aluminum salt catalystcomprises aluminum acetate.

Aspect 27: The method of any one of aspects 20-23, wherein the aluminumcatalyst is aluminum produced from an aluminum electrode at a voltagefrom 20V to 100V.

Aspect 28: The method of any one of aspects 20-27, wherein the secondvolume of aerogel is at least 70% of the first volume of the gel.

Aspect 29: The method of any one of aspects 20-28, wherein the step ofdrying the gel in gas comprises exposing the gel to gas having atemperature from about 70° C. to about 120° C.

Aspect 30: The method of any one of aspects 20-29, wherein the step ofdrying the gel in air comprises exposing the gel to gas having atemperature from about 80° C. to about 90° C.

Aspect 31: The method of any one of aspects 20-30, wherein thecrosslinking takes place in a solvent having a pH of from about 3 toabout 7.

Aspect 32: The method of any one of aspects 20-31, wherein thecrosslinking takes place in a solvent having a pH of from about 4 toabout 6.

Aspect 33: The method of aspect 32, wherein the solvent comprises water.

Aspect 34: The method of any one of aspects 20-33, wherein the molarratio of the polyhydroxy benzene compound to formaldehyde in thecrosslinking step is from about 1:1 to about 1:4.

Aspect 35: The method of any one of aspects 20-34, wherein the methodfurther comprises the step of modifying the aerogel with a chemicallinker and a signaling moiety.

Aspect 36: The method of aspect 35, wherein the chemical linker is boundto both the signaling moiety and the aerogel.

Aspect 37: The method of aspect 35, wherein the signaling moietycomprises a detection portion and a target binding portion.

Aspect 38: The method of aspect 37, wherein the detection portioncomprises fluorescence resonance energy transfer (FRET).

Aspect 39: The method of aspect 37, wherein the target binding portioncomprises a RNA molecule that binds to a target.

Aspect 40: An aerogel produced by the method of any one of aspects20-39.

Aspect 41: The aerogel of aspect 40, wherein the aerogel is capable ofabsorbing up to ten times its mass of a polar liquid or a non-polarliquid.

Aspect 42: A method comprising the steps of: a) providing the aerogel ofany one of aspects 1-19 or 40-41; and b) modifying the aerogel with achemical linker.

Aspect 43: The method of aspect 42, wherein the chemical linker isfurther modified with a signaling moiety.

Aspect 44: The method of aspect 43, wherein the chemical linker is boundto both the signaling moiety and the aerogel.

Aspect 45: The method of aspect 43, wherein the signaling moietycomprises a detection portion and a target binding portion

Aspect 46: The method of aspect 45, wherein the detection portioncomprises fluorescence resonance energy transfer (FRET).

Aspect 47: The method of aspect 45, wherein the target binding portioncomprises a RNA molecule that binds to a target.

Aspect 48: A method comprising a) incubating a sample obtained from asubject with the aerogel of any one of aspects 10-19; and b) determiningthe presence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel, wherein the presenceof the biomarker indicates the subject has a biological condition,wherein the absence of the biomarker indicates the subject does not havea biological condition.

Aspect 49: The method of aspect 48, wherein the signaling moietyprovides a positive signal in the presence of the biomarker.

Aspect 50: The method of aspect 49, wherein the positive signal is afluorescent signal.

Aspect 51: The method of any one of aspects 48-50, wherein the biomarkeris a nucleic acid, protein or metal.

Aspect 52: The method of aspects 49, wherein the nucleic acid is miRNA.

Aspect 53: The method of any one of aspects 48-52, wherein the targetbinding portion binds to the biomarker.

Aspect 54: The method of aspect 53, wherein the target binding portioncomprises a RNA molecule.

Aspect 55: The method of any one of aspects 48-54, wherein thebiological condition is an infectious disease, autoimmune disease,radiation exposure, or a genetic disorder.

Aspect 56: The method of any one of aspects 48-55, wherein the sample isblood.

Aspect 57: A method of detecting comprising the steps of: a) incubatinga sample with the aerogel of aspect 9; and b) detecting the presence orabsence of a biomarker for a biological condition in the sample usingthe signaling moiety of the aerogel.

Aspect 58: The method of aspect 57, wherein detecting the presence ofthe biomarker comprises a positive signal provided from the signalingmoiety of the aerogel.

Aspect 59: The method of aspects 57 or 58, wherein detecting the absenceof the biomarker comprises a negative signal or lack of signal providedfrom the signaling moiety of the aerogel.

Aspect 60: The method of any one of aspects 57-59, wherein the sample isblood.

Aspect 61: The method of any one of aspects 57-60, wherein the biomarkeris a nucleic acid, protein or metal.

Aspect 62: The method of aspect 61, wherein the nucleic acid is a miRNA.

Aspect 63: A device comprising the aerogel of any one of aspects 1-19 or40-41.

Aspect 64: The device of aspect 63, wherein the device is a medicaldevice.

Aspect 65: The device of aspect 63, wherein the device is a waterpurification device.

Aspect 66: The device of aspect 63, wherein the device is a chemicalseparation device.

Aspect 67: The device of aspect 63, wherein the device is an electricaldevice.

EXAMPLES

A. Aerogels and Carbon Foams

Four different types of carbon foam were tested C4501, C4502, BQ001,BQ001 hydrophobic. C4501 and C4502 were synthesized with aluminumacetate-deionized water solution that had been allowed to mix for onehour before polyhydroxy benzene and formaldehyde were added, mixedcompletely and allowed to cure at 90° C. They were then dried beforebeing carbonized in an inert enviorment at approximately 1050° C. BQ001was synthesized in a similar manner except the polyhydroxylbenzene-formaldehyde-aluminum acetate-deionized water solution wasabsorbed into and filled the pore volume of an alumina felt. BQ001hydrophobic was synthesized in a similar manner to BQ001 except it wasrendered hydrophobic after carbonization. All the experiments wereperformed in a 3-electrode system (FIG. 1), the approximated area of thecarbon foams tested were 1.4 cm².

The first set of experiments consisted in the study of theelectrochemical performance of the carbon foams in two differentelectrolytes: one aqueous (0.5M H₂SO₄) and one non-aqueous (1M LiClO₄).The advantages of using one versus the other is that an aqueouselectrolyte can give higher conductivity and are environmentallyfriendly; a non-aqueous electrolyte, although it has a lowerconductivity, can allow for a wider voltage range for the tests.

FIGS. 2A, 2B, and 2C show the cyclic voltammetry profiles in terms ofcapacitance (farads/g) vs. potential at various scan rates, for C4502,C4501 and BQ1001 respectivley tested in 0.5M H₂SO₄. From this test BQ001is the sample that presents a higher capacitance comparing with C4502and C4501 that show very similar performance.

FIG. 3a shows the Nyquist plot for real and imaginary impedance of thethree samples, C4502 and C4501 present similar resistance, whereas BQ001presents lower impedance comparing with the other two samples, whichindicates this sample has higher conductivity. FIG. 3b shows thedischarge profiles normalized to specific capacity (mAh/g), similar toimpedance, C4501 and C4502 show similar discharge profiles, while BQ001has a higher specific capacity (amount of charge that can be stored)when compared to the other two samples.

FIGS. 4A, 4B, 4C, and 4D show the cyclic voltammetry profiles normalizedby the scan rate and the mass (capacitance) of the samples tested in 1MLiClO₄ at various scan rates. C4501 and C4502 seem to have differentelectrochemical performance in non-aqueous electrolyte, where C4501presents a higher capacitance comparing with C4502. FIG. 5A shows BQ001hydrophobic shows a better electrochemical behavior than BQ001, althoughthere is more scan rate dependence in BQ001 hydrophobic than BQ001.

FIGS. 5A and 5B show the discharge profiles of the four samplesdescribed on FIGS. 4A, 4B, 4C, and 4D, similar to the cyclic voltammetryprofiles, C4501 and BQ001 hydrophobic present a higher specific capacity(amount of charge that can be stored) comparing with the rest of thesamples.

The second set of experiments aimed to polymerize conducting polymer(Polypyrrole) on the carbon foam in other to increase the capacitance,creating a composite material that can store higher amount of charge.Two different deposition charges, one is 2.68 C and the other 13.4 C (5times), were selected. Charge is related to the amount of polymergetting polymerized (mass deposited), although this relationship is notstrictly linear as expected in an ideal case.

In aqueous media BQ001 presented a higher capacitance comparing with therest of the samples (FIG. 2), although in order get the setup of theconditions right, C4501 was used because there is more of this samplethan the BQ001.

FIGS. 6A and 6B shows the cyclic voltammetry profiles of C4501 samplebefore (FIG. 6A) and after (FIG. 6B) the polymer deposition for 2.68 C,the latter shows an improvement in capacitance, as well as a significantreduction in the impedance (Nyquist plot, shown in FIG. 6C). Polymermass deposited: 2.29 mg, total mass of the substrate before deposition:22.64 mg.

FIGS. 7A and 7B show the cyclic voltammetry profiles of C4501 samplebefore (FIG. 7A) and after (FIG. 7B) the polymer deposition for 13.4 C.For this experiment the deposition profile was slightly different, thecurrent was ramped down from 14 to 10 and finally to 6 mA to accomplishthe deposition within the ideal deposition potential for pyrrole andtrying to avoid any overoxidation of the polymer that can cause adecrease in the performance of the composite material. The CV profileafter the deposition presents a significant improvement in thecapacitance when compared with the capacitance of the carbon foam byitself. There is also a reduction in the resistance (Nyquist plot, shownin FIG. 7C). Polymer mass deposited: 3.21 mg, total mass of thesubstrate before deposition: 23.62 mg.

Carbon foams have been tested on different electrolytes (standards forcarbon materials) and concentrations to identify in which one showsbetter electrochemical characteristics, it seems 0.5M H₂SO₄ is the bestone to study the samples.

Polymerizing the conducting polymer (Pyrrole) on the carbon foam is thentested. SEM micrographs show the polymerization is definitely possible.Identifying the ideal amount to avoid clogging the pores of the foam canbe helpful because this can likely cause a decrease in the performanceof the carbon foam after depositing polypyrrole.

These same experiments can be performed with a carbon foam sheet and canavoid some of the ion diffusion limitations seen in some of the cyclicvoltammetry plots.

FIGS. 8A and 8B show the comparison with other carbon materials. Thefact that the carbon foam shows a Capacitance (amount of charge stored)of about 100-125 F/g for the low scan rates is significant, because notall the carbon materials (mesoporous, activated carbon) depending on theconditions can reach such a high capacitance.

FIGS. 9A and 9B show that organic solvents have a lower conductivitycomparing with aqueous solvents, which is part of their limitations, soit is expected that under these conditions the electrochemicalperformance of the carbon foam can be lower than in aqueous solutions.However, organic solvents allow for a wider voltage range since they arenot limited by the decomposition voltage of water (1.23 to -0.83 V).

FIGS. 10A and 10B show that KOH is not necessarily a good option forthis material.

FIGS. 11A-11D show the cyclic voltammetry polymerization of pyrrole oncarbon foam. SEM micrographs show the typical cauliflower structure onthe surface, characteristic from polypyrrole deposited byelectrochemical polymerization.

Porous resorcinol-formaldehyde foams have been studied since 1989.However, these materials can exhibit significant and sometimescatastrophic shrinkage when dried at ambient conditions without anadditional organic solvent exchange step. In some instances, thedisclosed process requires no organic solvent exchange step and shrinksapproximately 3-4 percent when dried in air at approximately 90° C.Drying at lower temperatures would more than likely produce a similarproduct with a longer drying time. Additionally, the material createdwith this process is lyophilic as well as extremely hydrophilic. Somesamples have been made that can absorb more than 16 times their weightin water with most samples absorbing approximately 9 times their weightand can experience multiple wetting-drying cycles without significantdegradation. These qualities allow for processing of driedresorcinol-formaldehyde foam which heretofore was not possible with thecurrent state of the art. Additionally, after appropriate conditioning,the material became extremely hydrophobic. An example of appropriateconditioning is drying under heat in excess of 100° C. in the presenceof a desiccant.

This process accomplishes this through the use of novel catalyst,aluminum salts, which, as yet, have not been evaluated outside of thisart. By varying the concentration of catalyst, various pore sizes can beachieved. This process is tunable across a range of pH values, catalystconcentrations and constituent ratios. Varying one or more of these canproduce foams with different pore sizes distributions, absorptioncharacteristics, density and possibly carbon yield after pyrolysis.

The open celled foams known in the art had a solidification time of atleast 12 hours. The art described here has a solidification time of aslittle as two hours. If further curing is necessary, it can to a limitedextent, be accomplished during the drying step. These twocharacteristics could lead to a continuous process that incorporates themixing, curing and drying of the material as opposed to the currentstate of the art batch process.

The material itself is a light orange to dark red, porous phenolicmaterial with very low bulk density. The void space inside the materialis interconnected and made up of pores that range from sizes too smallto see under a 50X microscope to several millimeters.

B. Monitoring Device

The U.S. Department of Defense requires infectious disease in vitrodiagnostic (IVD) capabilities that are operationally suitable for use infar forward military environments and operationally effective versus awide range of threats. Current single use disposable Lateral FlowImmunoassay-based diagnostic tests have many desirable operationalsuitability characteristics (low cost, minimal training, lightweight,results in 15 minutes, eye readable results, and long shelf life at roomtemperature) but lack sufficient sensitivity to be clinically useful formost infectious diseases. Current nucleic acid amplification-baseddiagnostic tests provide adequate sensitivity for some diseases but areslow (>30 minutes), more complex, are not compatible with many hostresponse biomarker-based diagnostic approaches and have a high cost pertest. The High Sensitivity, Low Complexity, Multiplexed DiagnosticDevices topic seeks to develop novel approaches that will fundamentallyimprove sensitivity while maintaining desirable operational suitabilitycharacteristics. Furthermore, novel approaches will be needed toincorporate multiple analytical approaches into a single platformtechnology to provide clinical utility across a broad range ofetiological agents (i.e., intracellular organisms, parasites, etc.),diseases and clinical sample types and to provide information to supportforce health protection decision making.

1. Dengue Virus

The disclosed technology can be used to detect any number of things,including viral infections. An example is detection of the Dengue virus.The Dengue virus has four variants DENV1-4, which have a positive singlestrand RNA genome that directly translates 10 proteins. It is a memberof the genus Flavivirus, a genus which also includes such viruses asWest Nile virus, yellow fever virus, and Japanese encephalitis, amongothers. Dengue virus used to be restricted to tropical and subtropicalregions, however the exposure region is expanding, affecting 2.5 millionpeople in 110 countries. Of the people infected with Dengue, on average˜500,000 will have the potential to develop dengue hemorrhagic fever ordengue shock syndrome.

Dengue is transmitted via mosquito, as such, the virus is endemic totropical climates. The limiting factor for detecting live virus is theneed for the infection to reach a critical viral load in the host. Oneof the current, and most accurate, strategies for detecting infection isRT-PCR of the viral RNA. While highly sensitive, the method does notlend itself to field work, particularly in tropical regions. An attemptto improve this technology is a variation of RT-PCR, recombinasepolymerase amplification (RPA), utilizes a fluorescence probe andisothermic temperatures to detect DENV RNA in as little as 3 minutes.This allows for portability, but still relies on viral titer to meet athreshold. Therefore, while the readout is rapid and the device isportable, the time from infection to detection is still an average of 5days. One method to shorten detection time is to detect changes incirculating miRNAs as a result of infection.

A previous study found that circulating cytokine levels in infectedpatients could be detected as early as 6 hours post infection. Thecytokine production is heavily regulated at the mRNA level by microRNAs(miRNAS), 22-25 nucleotides in length. The changes in miRNA levels as aresult of infection occur upstream to changes in cytokine production,thereby shortening the detection time. The study identified a biomarkerof 15 differentially expressed miRNAs, 11 downregulated and 4upregulated, in response to DENV2 (and most likely the other DENVvariants) infection.

Detection of miRNA in blood, saliva or urine would require either acentralized laboratory, or a novel portable dipstick assay withsensitivity to nucleic acids exceeding the current capabilities ofnitrocellulose lateral flow assays.

2. Lateral Flow

Lateral flow immunochromatographic assays have been used to detect awide variety of antigens in biofluids for decades. Commonly implementedas a dipstick or fingerprick assay, the most familiar application of thetechnology may be the common pregnancy tests which detect HCG hormonesin the 1 ng/mL range.

The architecture of a traditional lateral flow dipstick is depicted inFIGS. 12A, 12B, and 12C. The sample is introduced to the sample pad. Thetreated sample migrates from this region past the conjugate pad, where acontrast-introducing particulate conjugate (either magnetic,colorimetric, or color-shifting) is mobilized from dry form toco-migrate with the sample elution. The conjugate particle is decoratedwith antigen or antibody, depending on the format of the test and theanalyte. As the sample and conjugate particle co-migrate down thenitrocellulose membrane, they pass a control line and a test line. Thetest line is encountered first, and is decorated on the surface of thenitrocellulose membrane with antigen or antibody to bind the analyteparticle, often in the form of a sandwich assay. The bound presence ofconjugate particles here represents a positive assay for presence of theanalyte. The control line is decorated to nonspecifically bind conjugateparticles without requiring the presence of the analyte; conjugateparticles here confirm that the system is functioning at the basiclevels of performance.

Traditional lateral flow assays rely upon colored latex microparticlesor plasmonically colored gold nanoparticles to provide anon-quantitative result. While historically these assays were read byambient light, as in the case of a home pregnancy test, there have beenrecent developments of quantitative assays with laser illuminationelectronic readout devices. In most cases, these techniques are limitedto traditional colorimetric assays of gold, silver or latexnanoparticles. Beyond quantitation over a limited range, automatedreader technology provides little benefit in terms of sensitivity overreading a lateral flow assay by eye, as scatter/background signalbecomes the dominant limiting factor when illumination power isincreased. The introduction of upconverting phosphors to lateral flowhas provided a relatively background-free detection scheme in recentyears, but due to the low diffusion constant of the phosphor-ladenupconverting micro-particles, the technique generally requires wetsample prep to achieve high sensitivities. The great benefit of lateralflow is the lack of sample prep or fluidics, which allows for field use.As a result, up-converting lateral flow assays are fundamentallylimited, and, as-of-now, an unrealistic option for a field-portabledevice.

Detection of nucleic acids associated with Dengue infection was recentlyperformed in a small, portable lateral flow format withoutamplification. This work utilized traditional nitrocellulose substratetechnology and represented the first published use of unamplified Denguenucleic acids in a lateral flow format. While this is an important stepin detecting Dengue sans amplification, the sensitivity of theexperiment was hampered by high background caused by the use ofnitrocellulose as the substrate, as concluded by the study's authors(FIG. 13A and 13B).

Lateral flow test strips can also utilize is Förster (alternativelyfluorescence) resonance energy transfer, or FRET. FRET relies upon adonor fluorophore, in this case permanently bound to the control andtest regions of the strip, which is excited upon illumination. Uponbinding of an acceptor fluorophore tagged analyte, the excited donor maynon-radiatively transfer its excitation energy to the acceptorchromophore, and the system emits at the wavelength associated with thisacceptor, rather than that of the originally excited donor. FRET orrelated phenomena are routine methods for the detection of ions, smallmolecules, proteins or nucleic acids. The model used to describe FRET isFörster theory, the underlying principle of which is based on transitiondipole-dipole interactions between the excited donor and acceptor. Thisinteraction has a distance dependence of 1/R6, where R is the distancebetween the donor and acceptor. The efficiency of transfer is thereforehighly dependent on distance, and FRET pairs can therefore be utilizedas extremely sensitive assays for binding.

Traditionally, FRET has suffered two major drawbacks. First, it is atechnique whose fundamental mechanism is extremely sensitive, but whosefinal sensitivity is limited by sources of noise and background, as itis essentially a ratiometric calculation on low level light signals.Second, FRET traditionally requires advanced optical setups utilizingphotomultiplier tubes or cooled CCD cameras.

3. Increased Sensitivity with Novel Aerogel Substrates

A phenolic aerogel was developed via an air dried processing techniquewhich can be made up of either purely phenolic, purely carbon or anystate in between while remaining wettable enough to act as a lateralflow substrate. Additionally, the aerogel-based foam has demonstratedtunability to a variety of densities and pore sizes which can be used tocreate materials that are very efficient wicking agents for a widevariety of fluids. The foams can remove suspended particles whilewicking due to the filtering action of the pore structure.

Given the tunability of the pore structure and surface conditions,aerogel makes an attractive alternative to many of the systems currentlyused in lateral flow assays, including nitrocellulose. Nitrocellulose isa negatively charged porous media that is used in a wide variety oflateral flow assays. However, nitrocellulose presents a number ofdisadvantages. It has a high scattering coefficient which can causebackground signal in any assay, and is a particular problem for FRET.Because the absorption coefficients of aerogels can be tuned from asignificant absorber to a nearly perfect absorber when carbonized,aerogels can be made to exhibit extremely low background scattering andauto fluorescence levels.

Furthermore, the aerogel yields a material better suited to lateral flowdecoration and nucleic acid immunoassaying than nitrocellulose. Whilebinding to nitrocellulose is poorly understood, it appears to bindhydrophobically. This is not ideal when working with oligonucleotidessince these tend to associate poorly with hydrophobic surfaces and thehydrophobic binding can affect the shape of the bound molecule whichcould cause it to either behave unpredictably or denature entirely. Incontrast, the aerogel system proposed here is a polymer that can rangein color from light orange to black and presents a high density ofhydroxyl groups, which can be used as covalent binding sites.

4. Prepare a Range of Aerogel Formulations Suitable for Lateral FlowFRET use

Aerogels are open cellular foams known for extremely high porosity andsurface area. Originally developed in the 1980′s, phenolic aerogels areformed from a metal ion catalyzed condensation reaction of rescorcinolwith formaldehyde into a cross-linked network of spheres which can beheated to over 1000° C. in an inert environment to create a carbon foamof identical dimensions.

These materials have shown great promise but have suffered from a numberof processing and durability limitations, for example the structureshrinks catastrophically when dried due to capillary forces. To preservethe structure, expensive and difficult processes are required such asnonpolar solvent exchange, freeze drying or super critical CO₂ washing.Recently, a new catalyst formula has been developed for a phenolic foamprocessing that can be air dried and subsequently processed using eitherwet chemistry or heat treatment under various conditions. The pore size,pore size distribution and wicking characteristics have been shown to bereproducibly alterable by varying the ratios of constituent partswithout affecting the underlying chemical structure.

The current study involves a) optimizing chemistry of the material toprovide an optimized pore size to facilitate wicking while exhibitingthe highest possible visible surface area and b) optimizing the heattreatment to reduce the noise signal while maintaining an acceptablenumber of binding sites.

i. Optimizing Chemistry of the Material to Provide an Optimized PoreSize

The pore size can be altered by varying the ratio of resorcinol tocatalyst while maintaining the ratio of resorcinol to formaldehyde andresorcinol to water. The optimal pore size is one that effectively wicksthe analyte solution through the pore space without filtering theanalyte while providing a large, non-shadowed, surface area. The wickingcan be evaluated by introduction of analyte solution into the materialwith various pore sizes. In each case, the amount of fluid absorbed andthe wicked height can be measured. The available surface area for eachpore size can be directly labeled with a fluorophore and excited using alaser. Increased fluorescent response can be indicative of an increasedsurface area, assuming the number of functional groups is held constant.

This can be expanded upon by the introduction of actual blood to judgethe material's ability to remove extraneous matter such as red bloodcells. A layered pattern of size-exclusion layers is envisioned toeffectively remove large solids and improve the clarity of the test.

ii. Optimizing the Heat Treatment

The number of binding sites (hydroxyl groups) present on the materialcan first be established in a fully cured sample prior to heat treatmentand in a fully carbonized sample that has no binding sites present. Autoflorescence can also be measured for these samples. Samples can beproduced and heat treated to higher temperatures in 100° C. increments.These samples can both be tested for hydroxyl group density andautofluorescence as well.

5. Functionalize and Optimize Aerogel for FRET (SRI, RMD)

The oligonucleotide probes to be covalently linked to the functionalizedaerogel can be modified to have donor and acceptor fluorescent probes atthe 5′ and 3′ ends respectively. These probes can allow for theutilization of FRET, whereby the donor fluorophores transfer theirexcited state to the excitation energy level of an acceptor fluorophore.The resultant emission intensity change upon binding is captured anddigitized into a quantifiable signal. Because of this energy transfer,the system can be multiplexed to use one excitation wavelength totransfer energy to a handful of potential acceptor fluorophores. CyanFluorescent protein, or CFP, is the most versatile donor as it canexcite both green and red fluorescent protein (GFP and RFP) acceptors.However, the size of these proteins is not conducive to binding freemiRNA.

Listed below in table 1 is a list of common donor/acceptor pairs, withfluorescein being the most versatile donor.

TABLE 1 Common donor/acceptor pairs Donor Acceptor R_(a) (Å) FluoresceinTetramethylrhodamine 55 IAEDANS Fluorescein 46 EDANS Dabcyl 33Fluorescein Fluorescein 44 BODIPY FL BODIPY FL 57 Fluorescein QSY 7 andQSY 9 dyes 61

The proper alignment of the donor and acceptor fluorophores occurs whenthe complimentary RNA strand binds the probe, locking the orientation.Use of a common donor simplifies the design by necessitating only oneexcitation wavelength. A diagram of the proposed probe-RNA binding andsubsequent FRET can be seen in FIG. 15.

Initial characterization of an aerogel substance by optical study:Samples of the aerogel can be examined for their suitability forchemical functionalization by Fourier Transform Infrared Spectroscopy[FTIR]. The surface density of hydroxyl groups on the convoluted foldsof the aerogel can be analyzed as a primary determinant of assayefficiency.

The appropriate sample preparation technique for the aerogel samples isto grind them to a fine powder and examine each sample by the AttenuatedTotal Reflection [ATR] sample handling technique. The intensity of thehydroxyl group absorption (3550-3200 cm⁻¹; a broad, strong signal) inthe FTIR as a function of carbonization temperature in 100° C.increments to develop an understanding of the density of phenol hydroxylgroups available for chemical reaction and chemical derivation to attachsignaling oligonucleotides. In FIG. 4A, how to ascertain the reactivityof the phenolic hydroxyl groups by treating the aerogel sample withacetyl chloride in an appropriate chlorocarbon solvent (such asmethylene chloride or chloroform) is shown. With FTIR, the amount ofhydroxyl group absorption remaining after chemical reaction with acetylchloride and the appearance of the ester carbonyl absorption can bemeasured. The intensity of the ester carbonyl absorption (1750-1735cm⁻¹; a sharp, strong signal) will be the reciprocal of the decrease inintensity of the phenol hydroxyl group absorption.

The samples can be further characterized for scattering andautofluorescence at FRET excitation wavelengths, as well as structuralintegrity and retention of wicking characteristics. Several formulationsoptimized to provide the best compromise between available reactivehydroxyl functionality, low autofluorescence, reduced scatteringbackground, and structural integrity can be chosen for use in thechemical derivatization studies.

Derivatization of the aerogel: A number of chemical techniques can beused to derivatize the aerogel substrate for the attachment of asignaling moiety such as miRNA. One method is used in the context ofoligonucleotide conjugation to inorganic and biological substrates andis known as ‘copper free click chemistry’. This involves the reaction ofan organic azide attached to the aerogel substrate by an ester,carbonate or carbamate group with a strained and reactive triple bondattached to a signaling oligonucleotide. Click chemistry is a clean andhigh yielding method for modular derivatization. The success of thesereactions can be followed by FTIR to examine the absorptions associatedwith ester formation (1750-1735 cm⁻¹), the azide group (2210-2200 cm⁻¹)and the triazole product of the reaction (1580-1550 cm⁻¹, 1490-1410cm⁻¹) between the azide and triple bond.

This process is illustrated in FIG. 16A. The unmodified aerogelsubstrate (1) is reacted with the organic azide (4) by formation of anester bond through the reaction of the acid chloride group in 4 with theavailable phenolic hydroxyl groups on 1 to give 5, the aerogel modifiedwith the organic azide. Likely solvents for this reaction includedichloromethane (CH₂C₁₂) or chloroform (CHCl₃).

In FIG. 16B, the reaction of 5 with the octyne click chemistry partner 6will give aerogel substrate modified with the oligonucleotide detector7. This reaction should take place at ambient temperature or with mildheating (not more than 100° C.); a solvent that can accommodate both theaerogel 5 and octyne modified oligonucleotide 6 would be the polaraprotic solvent such as dimethylformaide (DMF) or acetonitrile.

The required octyne-derivatized oligonucleotide detector 6 can beprepared from a commercially available octyne by a method disclosed inUS 2013/0066063 A1. This method is very convenient because it disclosesexactly the use of the starting material and describes how this compoundcan be derivatized with short miRNA sequences prepared by standard solidphase nucleoside synthesis techniques. The short miRNA sequences can bereadily derivatized to incorporate the appropriate fluorophore acceptor/ emitter pair using standard methods.

Fluorescence evaluation: Samples functionalized with acceptorfluorophores can be evaluated for relative density of fluorophoreloading and detection efficiency. Aerogel samples can be mounted andilluminated with collimated light from a LED chosen for overlap with theexcitation envelope of the donor fluorophore. A spectrometer can beutilized (Acton 2100i) to couple isotropic light at a close distancewith matched objective lenses or alternatively a round-to-slit fiberbundle. Samples can be evaluated for total fluorescent yield anduniformity, and can be tuned to maximize yield by maximizing surfacearea and reaction site density, while minimizing the effect of shadowingdue to convolution and increased optical density upon carbonization.

6. Prepare Infectious Analytes or Substitute Model Systems with AcceptorFluorophore Tagging Chemistry Completed

The analyte preparation can be based on the Dengue biomarker miRNAsknown in the art. The 5 miRNA probes can be commercially synthesized tocontain the same 5′ donor, but unique 3′acceptors so that each can bedetected individually. A master mix of the miRNA probes can be made inexcess to saturate the available functional binding sites on theaerogel. To test the ability of miRNAs to bind the probes and allow forfluorescence, oligonucleotides can be synthesized based on the maturemiRNA sequences (obtained from miRbase.org). These synthesized oligoscan also be used to test the lateral flow, and wicking capacity of theprobe-coated aerogel so as to optimize the pore structure as describedabove.

Specifically, the 5 most significantly altered miRNAs can be used as anindicator of exposure to the Dengue Virus. Examples of proposed miRNAtargets are: heavily upregulated-miR-4290, -let-7e, -1290 and-33a; andheavily downregulated- miR-106b

The corresponding mRNA sequence target for each miRNA, fluorescentlylabeled, can be attached to the aerogel. The binding of the miRNA to itstarget sequence can confer a conformational change to the fluorescentprobe, and using FRET can allow for detecting binding via emission ofthe acceptor fluorophore. The extent of the signal can be digitized andreported as a measure of the abundance of miRNA in the sample. Thedevice can provide a truly portable, no processing method of detectingDENV infection as close to the onset as possible by detecting changes inthe levels of circulating miRNA.

7. Perform Bench Testing of Optical Detection Scheme and Refine forMiniaturization

The field portability and eye readability of a multiplexed assay eitherrequires a complex pattern and/or color scheme to be subjectivelyanalyzed by untrained users, or a small, inexpensive and robustbattery-operated electro-optical reader system which quantitativelyinterprets results and presents the user with reduced data. The finalprototype tested in Phase II and beyond will include one of two methodsof multiplexing. The first is a led or laser array and a matchingavalanche photodiode array, with an array of corresponding filters whichare slid along a simple linear encoder, thereby allowing for digitalreadout of each fluorophore individually in each well. The second methodinvolves a small spectrometer chip developed via holographic gratingtechnology. This chip allows for high efficiency spectral analysis in acompact, low cost silicon-based package. This single chip is suited tothe multiplexing of analytes in a single well as limited only by thefluorescent label.

In this task, illumination by laser and LED and readout by avalanchephotodiode can be evaluated for technical feasibility and lower limit ofsensitivity of the aerogel FRET assay. Illumination can be adjustablebetween collimated and focused at a distance of 50 mm, and presented tothe aerogel at both 45° and 0°. Titrations of prepared miRNA analytescan be presented to the aerogel and remain unrinsed.

Filtration of LED light can be compared with technologies filtering morecollimated laser light, and an effective solution to filtering will bedetermined. If no filter media can be found to effectively allow for asensitive FRET assay, then spectrometer-on-chip integration can proceedto enable full scale prototyping.

A wide variety of avalanche photodiodes (APDs) are arrayable on chipsless than 400 microns in thickness and are biased with less than 40 Vwhile providing gains in excess of 10⁶. These photodiodes can beevaluated for suitability to tiling.

Detecting one infectious agent (in this case miRNA characteristic toDengue infection can be considered successful if detection can beperformed at 10⁻⁹M, or two orders of magnitude more sensitive thanprevious Dengue nucleic acid detection studies. Work to increasesensitivity to clinically relevant levels (10⁻¹¹ to 10⁻¹⁵ M) can includenot only optimization of the aerogel labeling and the detection system,but possibly also the pre-concentration of nucleic acids similar to anorthosilicate concentration step.

8. Validate Suitability of Instrument for Multiplexing Multiple Analytesvia a Second FRET Pair and/or Physical Separation of Analytes in aMultiwall Plate Assay

Probes for a certain analyte can be fixed to the surface and theresultant fluorescent material can be tested as described above.However, miRNA fingerprints require that several fluorescent probes bindseveral types of miRNA for a successful assay. Given the wide variety ofprobes and donor/acceptor pairs available, using emission colors is aviable solution with the difficulty being resolving the various colorsbecomes more difficult as the number of colors increases. In this way, asingle assay is analogous to a full, multiplexed detector.

Tests can be run to detect the presence of multiple miRNA strands usingmultiple probe-acceptor/donor systems fluorescing multiple emissioncolors. Patterning the various probes, all of which use the same donoracceptor pair spatially across the material can also be an effectivesolution.

Various modifications and variations can be made to the compounds,composites, kits, articles, devices, compositions, and methods describedherein. Other aspects of the compounds, composites, kits, articles,devices, compositions, and methods described herein will be apparentfrom consideration of the specification and practice of the compounds,composites, kits, articles, devices, compositions, and methods disclosedherein. It is intended that the specification and examples be consideredas exemplary.

We claim:
 1. An aerogel comprising a matrix of a polyhydroxy benzenecompound crosslinked with formaldehyde, wherein aluminum acetate isdispersed within the aerogel, wherein the aerogel is dry and has a firstvolume, wherein the aerogel can be exposed to water and be re-dried inair while retaining at least 70% of the first volume.
 2. The aerogel ofclaim 1, wherein the aerogel is hydrophilic.
 3. The aerogel of claim 1,wherein the aerogel is hydrophobic.
 4. The aerogel of claim 1, whereinthe polyhydroxy benzene compound is resorcinol.
 5. The aerogel of claim1, wherein the molar ratio of the polyhydroxy benzene compound toformaldehyde in the aerogel is from about 1:1 to about 1:4.
 6. Theaerogel of claim 1, wherein the aerogel can be exposed to water and bere-dried in air while retaining at least 90% of the first volume.
 7. Anaerogel comprising a matrix of a polyhydroxy benzene compoundcrosslinked with formaldehyde, wherein aluminum acetate is dispersedwithin the aerogel, wherein the aerogel is dry and has a first volume,wherein the aerogel can be exposed to water and be re-dried in air whileretaining at least 70% of the first volume, wherein the aerogel isfunctionalized with a chemical linker, wherein the chemical linkercomprises a reactive moiety, wherein the chemical linker comprises anamine, an amide, a silane, an azide, or a thiol.
 8. The aerogel of claim7, wherein the functionalized aerogel further comprises a signalingmoiety, wherein the chemical linker is bound to both the signalingmoiety and the aerogel, wherein the signaling moiety comprises adetection portion and a target binding portion.
 9. A method of makingthe aerogel of claim 1 comprising the steps of: a) crosslinking apolyhydroxy benzene compound with formaldehyde in the presence ofaluminum acetate, thereby forming a gel having a first volume; and b)drying the gel in gas, thereby forming an aerogel having a secondvolume.
 10. A method comprising a. incubating a sample obtained from asubject with the aerogel of claim 8; and b. determining the presence orabsence of a biomarker for a biological condition in the sample usingthe signaling moiety of the aerogel, wherein the presence of thebiomarker indicates the subject has a biological condition, wherein theabsence of the biomarker indicates the subject does not have abiological condition.
 11. A method of detecting comprising the steps of:a. incubating a sample with the aerogel of claim 8; and b. detecting thepresence or absence of a biomarker for a biological condition in thesample using the signaling moiety of the aerogel.
 12. A devicecomprising the aerogel of claim
 1. 13. An aerogel produced by a methodcomprising the steps of: a. crosslinking a polyhydroxy benzene compoundwith formaldehyde in the presence of aluminum acetate, thereby forming agel having a first volume; and b. drying the gel in gas, thereby formingan aerogel having a second volume, wherein the aerogel is the aerogel ofclaim
 1. 14. An aerogel comprising a matrix of a polyhydroxy benzenecompound crosslinked with formaldehyde, wherein aluminum acetate isdispersed within the aerogel, wherein the aerogel is dry and has a firstvolume, wherein the aerogel can be exposed to water and be re-dried inair while retaining at least 70% of the first volume, wherein theaerogel is a functionalized with an alkyl group, an alkenyl group, or analkynyl group.